White Blood Cell Count and Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention in the Contemporary Era: Insights From the PARIS Study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry).

Elevated white blood cell (WBC) count is associated with increased major adverse cardiovascular events (MACE) in the setting of acute coronary syndrome. The aim of this study was to evaluate whether similar associations persist in an all-comers population of patients undergoing percutaneous coronary intervention in the contemporary era. In the multicenter, prospective, observational PARIS study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry), 4222 patients who underwent percutaneous coronary intervention in the United States and Europe between July 1, 2009, and December 2, 2010, were evaluated. The associations between baseline WBC and MACE (composite of cardiac death, stent thrombosis, spontaneous myocardial infarction, or target lesion revascularization) at 24-month follow-up were analyzed using multivariable Cox regression. Patients with higher WBC were more often younger, smokers, and with less comorbid risk factors compared with those with lower WBC. After adjustment for baseline and procedural characteristics, WBC remained independently associated with MACE (hazard ratio [HR] per 10(3) cells/μL increase, 1.05 [95% confidence intervals (CI), 1.02-1.09]; P=0.001), cardiac death (HR, 1.10 [95% CI, 1.05-1.17]; P<0.001), and clinically indicated target revascularization (HR, 1.04 [95% CI, 1.00-1.09]; P=0.03) but not stent thrombosis (HR, 1.07 [95% CI, 0.99-1.16]; P=0.10) or spontaneous myocardial infarction (HR, 1.03 [95% CI, 0.97-1.09]; P=0.29). The association between WBC and MACE was consistent in acute coronary syndrome and non-acute coronary syndrome presentations (interaction P=0.15). Increased WBC is an independent predictor of MACE after percutaneous coronary intervention in a contemporary all-comers cohort. Further studies to delineate the underlying pathophysiologic role of elevated WBC across a spectrum of coronary artery disease presentations are warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00998127

Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (from the Patterns of Non-adherence to Anti-platelet Regimens In Stented Patients Registry).

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for <14 days. Of the study cohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Author Manuscript: 2011 April 14Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.National Institutes of Health (U.S.) (GM 49039

Pneumothorax in COVID-19 Acute Respiratory Distress Syndrome: Case Series.

Objective The study aims to describe the clinical characteristics and outcomes of patients with COVID-19 related acute respiratory distress syndrome (ARDS) who developed pneumothorax. Design and setting A retrospective chart review was performed of the electronic medical record. Patients were included if they were identified as having confirmed COVID-19 as well as pneumothorax from March 16, 2020 to May 31, 2020. Patients\u27 demographic and clinical characteristics, mechanical ventilator parameters, lung compliance measurements and outcomes during hospitalization were collected. This case series was conducted in intensive care units at two large tertiary care centers within the Northwell Health System, located in New York State. Patients A total of 75 patients were identified who were predominantly male (73.3%) with an average age of 62.8 years. Thirty (40%) were Hispanic, 20 (26.7%) were White, 16 (21.3%) were Asian, and nine (12%) were Black. Common comorbid conditions were hypertension (52%), diabetes mellitus (26.7%), hyperlipidemia (32.0%), and chronic pulmonary disease (8, 10.7%). Measurements and main results Most of the patients were diagnosed with pneumothorax while on mechanical ventilation (92%) despite overall adherence with lung-protective ventilation strategies. Average tidal volume was 6.66 mL/kg) of ideal body weight. The average positive end-expiratory pressure (PEEP) was 10.83 (cm) H2O. Lung compliance was poor, with average peak and plateau pressures of 41.9 cm H2O and 35.2 cm H2O, respectively. Inpatient mortality was high in these patients (76%). Conservative management with initial observation had a success rate (73.3%) with similar mortality and shorter length of stay (LOS) on average. Significant factors in the conservatively managed group included lack of tension physiology, the smaller size of pneumothorax, lack of underlying diabetes, presence of pneumomediastinum, and not being on mechanical ventilation during diagnosis. Conclusion Despite overall adherence to best practice ventilator management in ARDS, we observed a large number of pneumothoraces during the COVID-19 pandemic. Conservative management may be appropriate if there are no clinical signs or symptoms of tension physiology and pneumothorax size is small

The EANM guideline on radioiodine therapy of benign thyroid disease

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients’ preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.</p

Protein domain movement involved in binding of belinostat and HPOB as inhibitors of histone deacetylase 6 (HDAC6): a hybrid automated-interactive docking study

DockIT is a tool for interactive molecular docking that can model both the local and global conformational response of the receptor to the docking of a ligand based on information from a molecular dynamics simulation. Using DockIT we have investigated the binding process of two histone deacetylase (HDAC) inhibitors to HDAC6: the nonselective approved drug belinostat and the preclinical HPOB. To model HDAC6’s conformational response to the binding of the inhibitors we performed a 200-nanosecond explicit-solvent molecular dynamics simulation on HDAC6. Unexpectedly the simulation revealed a domain movement that affects the size and shape of the binding pocket. Using automated docking and a rigid model for the inhibitors, the domain movement continuously adapts the pocket to the presence of the inhibitor. For both inhibitors, an intermediate binding site was found where it was partially inserted, with a hydrogen bond formed between the inhibitor’s hydroxamic acid and the Tyr745 side chain. Pushing the inhibitor deeper into the pocket over an energy barrier and re-engaging automated docking, a final binding pose resulted with a root-mean square deviation with its respective crystallographic pose of 1.0 Å for belinostat and 1.4 Å for HPOB. We believe our results mimic substrate recognition by the enzyme, with an initial partial binding of the acetyllysine residue with Tyr745. During binding a relay of hydrogen bonds occurs coordinating the orientation of the cap and the hydroxamic acid inside the pocket. The interaction between the cap and the surface of HDAC6 explains the reason for the hydroxamic acid warhead in HPOB binding in a flipped orientation compared to belinostat

Classification of coronary artery bifurcation lesions and treatments: Time for a consensus!

Background: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. Methods: The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. Results: A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. Conclusion: The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups. © 2008 Wiley-Liss, Inc

BAlloon expandable vs. SElf expanding transcatheter vaLve for degenerated bioprosthesIs: design and rationale of the BASELINE trial

Background: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. Methods: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient &lt;20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. Conclusions: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072)